The neonatal period is characterized by requirements for metabolic heat production and many other new energy demands as well. Therefore the rapid development of aerobic energy metabolism is essential to survival. The broad objective of this project is to understand the physiological stimuli and cellular mechanisms that control the perinatal development of cellular respiration and to relate these findings to the neonate's capacity for metabolic thermoregulation. We have shown a precipitous perinatal rise in the specific activity of substrate oxidation in liver and heart homogenates. The increase has two phases: an activation of existing mitochondria in the first six hours and a proliferation of mitochondria over a 24 hour time period. Existing evidence suggests the hypothesis that the change in oxygen availability may be the simulus for the proliferative increase in the number of functional mitochondria, while cAMP-mediated hormone action (catecholamines or glucagon) may modulate the maximum respiratory rates of mitochondria per se. To test this idea we will evaluate the effect of several possible initiating stimuli (po2' hypoglycemia, cold stress) on normal development of cellular respiration in newborn rats and rabbits, and will investigate the stage of development at which fetuses are competent to respond to the appropriate stimulus. In addition, studies will be carried out to elucidate the molecular mechanisms of action which mediate the increase in cellular respiration. The findings will then be related to the neonate's maximum capacity for a metabolic defense against cold stress. It is expected that the results will yield new information concerning the regulation of cellular respiratory capacity and mitochondrial biogenesis in mammals. The eventual application of these results to prescribing optimal environments especially for babies-at-risk, is an important long-range objective.